Autoimmune diseases are generally believed to be caused by the failure of the immune system to discriminate between antigens of foreign invading organisms (non-self) and tissues native to its own body (self). When this failure to discriminate between self and non-self occurs and the immune system reacts against self antigens, an autoimmune disorder may arise. Autoimmune diseases, or diseases having an autoimmune component, include rheumatoid arthritis, multiple sclerosis, systemic lupus erythromatosis (SLE), scleroderma, diabetes, inflammatory bowel disease, psoriasis and atherosclerosis. “Alloimmune diseases” are referred to herein as disorders such as graft versus host disease and tissue transplant rejection, in which an immune response against or by foreign, transplanted tissue can lead to serious complications or be fatal. In the treatment of these disorders, it is desired to prevent the body from reacting against non-self antigens.
Allogeneic hematopoietic stem cell transplantation (SCT) is a curative therapy for malignant and non malignant conditions. Unfortunately, a number of complications can occur due to SCT treatment. One major complication is diffuse lung injury, which occurs in 25% to 55% of SCT recipients and can account for approximately 50% of all SCT related mortality. Lung injury following SCT can be infectious or noninfectious and recent advances in treatment of infectious lung injury has reduced the incidence of this complication. However, an increase in pulmonary lung injury from non-infectious etiologies has been observed and non-infectious lung injury poses a significant clinical challenge, as it is associated with significant morbidity and mortality. One type of non-infectious lung injury is idiopathic pneumonia syndrome (IPS) which is defined as widespread alveolar injury following SCT without an active lower respiratory tract infection. It is considered a clinical syndrome with the pathogeneses and diagnostic criteria of this complication remaining undefined. The incidence of IPS ranges from 5 to 25% with a median onset of approximately 14 days and an overall day 100 mortality of 80% despite aggressive treatment therapies.
IPS encompasses a spectrum of clinical presentations and is thought to result from a diversity of lung insults, including toxic effects of myeloablative conditioning, immunologic cell-mediated injury, inflammatory cytokines, and occult pulmonary infections (Fukuda et al. (2003) Blood. 102(8): 2777). Lung biopsies in IPS show diffuse alveolar damage, organizing or acute pneumonia, and interstitial lymphocytic inflammation. The clinical presentation and radiographic findings do not differentiate between infectious and idiopathic pneumonia. Often infection needs to be excluded by bronchoalvelor lavage (BAL) or lung biopsy. Because IPS mimics infectious pneumonia, treatment regimes for IPS include supportive care measures in conjugation with broad-spectrum anti-microbial agents with or without intravenous therapy but responses are limited and the mortality of patients who develop this disease remains high.
IPS continues to cause transplantation-related morbidity and mortality despite advances in diagnostic methods for opportunistic infections and refinements in supportive care. IPS typically occurs early after SCT, therefore advances in transplantation medicine, such as the characterization and prevention of IPS could alter the spectrum of lung injury in patients who have undergone a hematopoietic stem cell transplant.